线粒体自噬调控前列腺组织中NLRP3炎症小体的表达在实验性自身免疫性前列腺炎大鼠中的作用机制

doi:10.3969/j.issn.1006-5725.2025.12.007

Abstract

Abstract:

Objective To investigate the mechanism of mitochondrial autophagy regulating the expression of NLRP3 inflammasome in prostate tissue in experimental autoimmune prostatitis（EAP）rats and to provide a theoretical basis for the study of new drug development. Methods A numerical table of 40 SD male rats was randomly divided into 8 groups. Namely， normal group （N）， model group （M）， rapamycin group （RAP）， rapamycin + mitochondrial autophagy inhibitor group （RAP+Mdivi-1）， autophagy inhibitor group （3MA）， mitochondrial autophagy inhibitor group （Mdivi-1）， Caspase1 inhibitor group （Caspase1）， NLRP3 inhibitor group （NLRP3）， 5 animals per group. After drug intervention， HE staining， immunofluorescence， colorimetry， and WB method were used to observe the relevant indexes. Results Compared with group N， the structural damage of prostate gland was obvious in group M. Compared with the M group， the prostate gland structure in RAP group， Caspase-1 group and NLRP3 group were improved. However， that in 3-MA group and Mdivi-1 group was not improved， and even destroyed more obviously. Compared with group N， the co-expression of LC3-II and LAMP-1 was enhanced， mitochondrial membrane potential was decreased， ROS release level was significantly increased in prostate tissue of rats in group M. Compared with the M group， the above indexes in RAP group and NLRP3 group were significantly improved. However， the above indexes in 3-MA group and Mdivi-1 group became worse. Compared with group N， the protein expressions of DRP1， PINK1 and Parkin in prostate mitochondria of rats in group M were increased， and the protein expressions of OPA1 was decreased. Compared with group M， the protein expressions of DRP1， PINK1 and Parkin in RAP group and NLRP3 group were significantly increased， while those in 3-MA group and Mdivi-1 group were significantly decreased. OPA1 protein expression was significantly decreased in the RAP group. The protein expression of Parkin in Caspase-1 group was decreased， but the protein expression of DRP1， OPA1 and PINK1 had no significant difference. Compared with group N， the protein expressions of LC3II/LC3I， Beclin1， NLRP3， ASC， Cleaced-Caspase1， Cleaced-IL-1β， and IL-18 in prostate tissue of rats in group M were increased， while the protein expressions of P62 was decreased. Compared with M group， LC3II/LC3I and Beclin1 protein expressions in RAP group and NLRP3 group were significantly increased， while those in 3-MA group and Mdivi-1 group were significantly decreased. Compared with M group， P62， NLRP3， ASC， Cleaced-Caspase1， Cleaced-IL-1β and IL-18 protein expressions in RAP group and NLRP3 group were significantly decreased， while those in 3-MA group and Mdivi-1 group were significantly increased. Compared with M group， the protein expressions of NLRP3， ASC， Cleaced-Caspase1， Cleaced-IL-1β， and IL-18 in Caspase-1 group were significantly reduced， but the protein expressions of LC3Ⅱ/LC3Ⅰ， Beclin1， and P62 were not statistically significant. Conclusions NLRP3 inflammatosome is involved in the progression of chronic prostatitis in EAP rats. Mitochondrial autophagy mediates the occurrence and development of prostatitis in EAP by regulating the activation of NLRP3 inflammasome in prostate tissue.

Key words: chronic prostatitis, mitochondrial autophagy, Pink1/Parkin pathway, NLRP3 inflammasome, inflammation

CLC Number:

R697.33

Liangxi LU,Haiwang LU,Wenjie WANG,Jun SHI,Zhimin HUANG,Bin BIN. To investigate the mechanism of mitochondrial autophagy regulating the expression of NLRP3 inflammasome in prostate tissue in rats with experimental autoimmune prostatitis[J]. The Journal of Practical Medicine, 2025, 41(12): 1816-1824.

Figures/Tables 10

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References 26

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组别	LC3-II/LAMP-1共表达水平	mtROS水平	线粒体膜电位
N组	3.941 ± 0.255	2.686 ± 1.191	5.895 ± 0.189
M组	7.006 ± 1.003^△△	32.611 ± 3.192^△△	0.575 ± 0.197^△△
RAP组	20.208 ± 1.248^▲▲	10.916 ± 1.342^▲▲	1.985 ± 0.271^▲▲
RAP+Mdivi-1组	13.771 ± 1.402^▲▲	35.126 ± 1.271	0.738 ± 0.101
3-MA组	3.225 ± 0.633^▲▲	42.046 ± 1.006^▲▲	0.122 ± 0.021^▲▲
Mdivi-1组	3.583 ± 0.404^▲▲	44.245 ± 3.362^▲▲	0.217 ± 0.125^▲▲
Caspase1组	7.593 ± 0.703	7.871 ± 1.385^▲▲	3.227 ± 0.162^▲▲
NLRP3组	13.735 ± 0.891^▲▲	4.366 ± 0.864^▲▲	4.779 ± 0.161^▲▲
F值	141.001	249.709	511.302
P值	< 0.001	< 0.001	< 0.001

组别	DRP1	OPA1	Parkin	PINK1
N组	0.206 ± 0.048	1.471 ± 0.157	0.304 ± 0.092	0.319 ± 0.116
M组	0.441 ± 0.063^△△	0.756 ± 0.121^△△	0.571 ± 0.089^△△	0.768 ± 0.101^△△
RAP组	1.114 ± 0.127^▲▲	0.282 ± 0.075^▲▲	1.287 ± 0.146^▲▲	1.431 ± 0.157^▲▲
RAP+Mdivi-1组	0.705 ± 0.092^▲▲	0.556 ± 0.090^▲	0.651 ± 0.138	0.986 ± 0.099^▲▲
3-MA组	0.222 ± 0.064^▲▲	1.231 ± 0.155^▲▲	0.229 ± 0.079^▲▲	0.266 ± 0.076^▲▲
Mdivi-1组	0.184 ± 0.043^▲▲	1.388 ± 0.18^▲▲	0.232 ± 0.082^▲▲	0.205 ± 0.054^▲▲
Caspase1组	0.349 ± 0.085	0.770 ± 0.10	0.397 ± 0.103^▲	0.715 ± 0.088
NLRP3组	0.595 ± 0.095^▲▲	0.731 ± 0.126	0.746 ± 0.123^▲	0.966 ± 0.137^▲▲
F值	76.512	51.333	52.693	77.849
P值	< 0.001	< 0.001	< 0.001	< 0.001

组别	LC3Ⅱ/LC3Ⅰ	Beclin1	P62
N组	0.287 ± 0.102	0.161 ± 0.058	0.928 ± 0.085
M组	0.851 ± 0.207^△△	0.424 ± 0.092^△△	0.585 ± 0.089^△△
RAP组	3.704 ± 0.336^▲▲	1.227 ± 0.131^▲▲	0.142 ± 0.037^▲▲
RAP+Mdivi-1组	2.003 ± 0.313^▲▲	0.728 ± 0.102^▲▲	0.313 ± 0.062^▲▲
3-MA组	0.414 ± 0.163^▲▲	0.188 ± 0.072^▲▲	0.957 ± 0.082^▲▲
Mdivi-1组	0.393 ± 0.101^▲▲	0.184 ± 0.041^▲▲	0.961 ± 0.099^▲▲
Caspase1组	0.999 ± 0.233	0.446 ± 0.078	0.564 ± 0.051
NLRP3组	1.783 ± 0.171^▲▲	0.649 ± 0.094^▲▲	0.410 ± 0.057^▲▲
F值	139.798	85.728	92.167
P值	< 0.001	< 0.001	< 0.001

组别	ASC	NLRP3	Cleaved-Caspase1	Cleaved-IL-1	IL-18
N组	0.052 ± 0.029	0.106 ± 0.069	0.220 ± 0.078	0.232 ± 0.071	0.163 ± 0.046
M组	0.486 ± 0.088^△△	0.887 ± 0.120^△△	1.095 ± 0.089^△△	1.305 ± 0.133^△△	0.912 ± 0.108^△△
RAP组	0.213 ± 0.051^▲▲	0.540 ± 0.114^▲▲	0.612 ± 0.126^▲▲	0.751 ± 0.122^▲▲	0.493 ± 0.120^▲▲
RAP+Mdivi-1组	0.451 ± 0.093	0.891 ± 0.116	1.015 ± 0.062	1.219 ± 0.138	0.932 ± 0.084
3-MA组	0.621 ± 0.071^▲▲	1.099 ± 0.100^▲▲	1.371 ± 0.163^▲▲	1.359 ± 0.235	1.212 ± 0.105^▲▲
Mdivi-1组	0.629 ± 0.083^▲▲	1.185 ± 0.207^▲▲	1.453 ± 0.162^▲▲	1.382 ± 0.166	1.211 ± 0.096^▲▲
Caspase1组	0.124 ± 0.053^▲▲	0.197 ± 0.088^▲▲	0.410 ± 0.111^▲▲	0.343 ± 0.122^▲▲	0.291 ± 0.061^▲▲
NLRP3组	0.096 ± 0.043^▲▲	0.198 ± 0.104^▲▲	0.422 ± 0.064^▲▲	0.256 ± 0.122^▲▲	0.310 ± 0.071^▲▲
F值	62.268	64.154	84.951	63.448	112.284
P值	< 0.001	< 0.001	< 0.001	< 0.001	< 0.001

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To investigate the mechanism of mitochondrial autophagy regulating the expression of NLRP3 inflammasome in prostate tissue in rats with experimental autoimmune prostatitis

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